DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application
Receipt of Applicant’s remarks and amended claims filed on June 11, 2026 is acknowledged.
Claims 1-2, 5-8, 19-21 are pending in this application.
Claims 3-4, 9-18, and 22-24 have been cancelled.
Claims 1, 5, 7, 19, and 20 have been amended.
All pending claims are under examination in this application.
Information Disclosure Statement
Receipt of the Information Disclosure Statement filed on June 11, 2026 is acknowledged. A signed copy attached to this office action.
Withdrawn Objections/Rejections
Claim Objections
The objection of claims 1, 5, and 7 because:
claim 1 contains an unnecessary comma (,) after “layer” has been withdrawn in view of the amendment to claim 1 to remove the comma;
claim 5 which depends from claim 1 recites the mucoadhesive layer comprises the “non-nanoparticulate macrolide”, however, claim 1 recites the mucoadhesive layer comprises a non-nanoparticulate macrolide thus the additional recitation is redundant has been withdrawn in view of the amendment to recite “The mucoadhesive layer according to claim 1, further comprising:
a cellulose derivative;
a plasticizer; and
optionally a colorant.”, as suggested by the Examiner; and
claim 7 does not read well has been withdrawn in view of the amendment to the claim to recite “The mucoadhesive layer according to claim 1, wherein:
the mucoadhesive polymer is an amphiphilic polymer, and the mucoadhesive layer further comprises hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), a plasticizer, and optionally a colorant; or
the mucoadhesive polymer is selected from the group consisting of crosslinked polyacrylic acid polymers and copolymers of methyl vinyl ether and maleic anhydride; and the mucoadhesive layer further comprises hydropropyl cellulose (HPC); ethyl cellulose (EC); a plasticizer; optionally a colorant.
Claim Rejections - 35 USC § 112
The rejection of claim 19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention because claim 19 recites the limitation "the macrolide immune suppressant", “the macrolide antibiotic”, and “the macrolide antifungal” in lines 2, 4, and 7, respectively and there is insufficient antecedent basis for these limitations in the claim has been withdrawn in view of the change in dependency to claim 2. . Claim 1, from which 19 depends recites “a non-nanoparticulate macrolide”.
Claim Rejections - 35 USC § 102
The rejection of claims 1-3, 5-6, 8, and 19-20 under 35 U.S.C. 102(a)(1) as being anticipated by Ashwathy et al. (Development and Chacterization of Buccal Film: Tacrolimus as a model drug, Journal of Medical Biomedical and Applied Sciences, 21 January 2019) has been withdrawn in view of extensive amendments to claim 1 to recite:
“wherein said non-nanoparticulate macrolide is present in said layer in a form of micronized macrolide and/or in a molecularly dissolved non-nanoparticulate form, wherein the micronized macrolide has an average particle size from 1 to 100 µm, and the molecularly dissolved non-nanoparticulate form is molecularly dissolved in a polymer matrix, and
wherein the mucoadhesive layer comprises a mucoadhesive polymer selected from the group consisting of (a) amphiphilic polymers and hydrophilic polymers, (b) poly(methacrylates). (c) crosslinked polyacrylic acid polymers. (d) copolymers of methyl vinyl ether and maleic anhydride, and (e) polymers comprising polyvinyl acetate and/or polyvinylpyrrolidone.”
Claim Rejections - 35 USC § 103
The rejection of claims 1-5 and 19 under 35 U.S.C. 103 as being unpatentable over McClain et al. (CA 2810842) in view of Kaurav et al. (Mucoadhesive Microspheres as carriers in Drug Delivery: a Review, International Journal of Drug Development and Research, April-June 2012, Vol 4, Issue 2) has been withdrawn in view of extensive amendments to claim 1 to recite:
“wherein said non-nanoparticulate macrolide is present in said layer in a form of micronized macrolide and/or in a molecularly dissolved non-nanoparticulate form, wherein the micronized macrolide has an average particle size from 1 to 100 µm, and the molecularly dissolved non-nanoparticulate form is molecularly dissolved in a polymer matrix, and
wherein the mucoadhesive layer comprises a mucoadhesive polymer selected from the group consisting of (a) amphiphilic polymers and hydrophilic polymers, (b) poly(methacrylates). (c) crosslinked polyacrylic acid polymers. (d) copolymers of methyl vinyl ether and maleic anhydride, and (e) polymers comprising polyvinyl acetate and/or polyvinylpyrrolidone.”
The rejection of claim 7 and 21 under 35 U.S.C. 103 as being unpatentable over Ashwathy et al. (Development and Chacterization of Buccal Film: Tacrolimus as a model drug, Journal of Medical Biomedical and Applied Sciences, 21 January 2019) in view of Nadh et al. (An Overview on Mucoadhesive Polymers for Buccal Drug Delivery, Int. J. Pharm. Sci. Rev. Res., 67(1), March-April 2021, Article No. 29, pages 178-186) has been withdrawn in view of extensive amendments to claim 1 to recite:
“wherein said non-nanoparticulate macrolide is present in said layer in a form of micronized macrolide and/or in a molecularly dissolved non-nanoparticulate form, wherein the micronized macrolide has an average particle size from 1 to 100 µm, and the molecularly dissolved non-nanoparticulate form is molecularly dissolved in a polymer matrix, and
wherein the mucoadhesive layer comprises a mucoadhesive polymer selected from the group consisting of (a) amphiphilic polymers and hydrophilic polymers, (b) poly(methacrylates). (c) crosslinked polyacrylic acid polymers. (d) copolymers of methyl vinyl ether and maleic anhydride, and (e) polymers comprising polyvinyl acetate and/or polyvinylpyrrolidone.”
Newly Applied Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 19 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 19, the phrase "in particular" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 5-8, 19 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Jenkins et al (US 2009/0252806 A1) in view of Schiraldi et al (4,713,243) and Lindsley et al (WO 2019/079783 A1).
Jenkins discloses a nanoparticulate dispersion of tacrolimus comprising
particles of tacrolimus having an effective average particle size of less than 2000nm (2 µm) and at least one surface stabilizer (claim 1).
Jenkins discloses that the nanoparticulate dispersion can be administered buccally, nasally, or topically and as a controlled release formulation.
Jenkins does not teach dispersion is present mucoadhesive layer as recited in claim 1.
Schiraldi discloses a controlled-releasing medicament-containing extruded single or multi-layered thin film as shown below:
A pharmaceutically acceptable controlled-releasing medicament-containing extruded single or multi-layered thin film, capable of adhering to a wet mucous surface, comprising a water soluble or swellable polymer matrix bioadhesive layer which can adhere to a wet mucous surface and which bioadhesive layer consists essentially of:
40-95% by weight of a hydroxypropyl cellulose having a molecular weight above 100,000,
5-60% of a homopolymer of ethylene oxide having a molecular weight from 3,000,000 to 5,000,000, 0-10% of a water-insoluble polymer selected from the group consisting of ethyl cellulose, propyl cellulose, polyethylene and polypropylene, and
2-10% of a plasticizer,
said film having incorporated therein a pharmaceutically effective amount of said medicament (claim 1).
It is noted that hydroxypropyl cellulose is an amphiphilic polymer.
Schiraldi discloses that its bioadhesive extruded film is so thin and flexible when wet as to be unobtrusive to the patient after it has been properly positioned and placed in the mouth (column 1, lines 17-20).
Schiraldi discloses that its film can be easily applied, has little or no mouthfeel, has good adhesion to the mucosal tissues and provides controlled release of the medicament and thus teaches that it is an effective and convenient intra-oral drug delivery system (column 2, lines 14-23). Since Jenkins also teaches that its nanoparticulate tacrolimus dispersion can be administered buccally as a controlled release formulation, it would have been obvious to one skilled in the art to use Schiraldi's bioadhesive extruded film to deliver Jenkins's tacrolimus buccally with a reasonable expectation that such bioadhesive film would be easily applied, would have little mouthfeel and good adhesion to the mucosal tissue while effectively providing controlled release of the tacrolimus in an unobtrusive way.
Regarding claim 2, it is note Tacrolimus is a macrolide immunosuppressant.
Regarding claim 5, as noted above, a water insoluble polymer, such as ethyl cellulose and propyl cellulose, and a plasticizer.
Regarding claim 8, the figures disclose dispersions of 10% of the nanoparticulate tacrolimus
Regarding claim 19, as noted above, tacrolimus is disclosed.
Regarding claim 20, as noted above, hydropropyl cellulose and ethyl cellulose are disclosed.
Regarding the instant tacrolimus contained in the mucoadhesive layer, Schiraldi teaches in claim 1 that the medicament is contained in the bioadhesive film, and the medicament may be incorporated into any or all of the layers (column 2, lines 52-56).
Thus, it would have been obvious to one skilled in the art prior to the effective filing date of the invention to include Jenkins's tacrolimus in the bioadhesive layer (instant mucoadhesive layer of claim 1) of Schiraldi's bioadhesive extruded film with a reasonable expectation of success.
Regarding the instant mucoadhesive polymer, Schiraldi's bioadhesive layer in its bioadhesive extruded film contains a homopolymer of ethylene oxide, which is instant mucoadhesive polymer (see Schiraldi's claim 1 shown above).
Regarding the instant cellulose derivative, Schiraldi teaches that its bioadhesive layer also contains a hydroxypropyl cellulose (instant cellulose derivative of claims 1 and 5).
Thus, Jenkins in view of Schiraldi teaches instant mucoadhesive layer comprising tacrolimus, a mucoadhesive polymer and a cellulose derivative.
Regarding the instant limitation "non-nanoparticulate", Jenkins in view of Schiraldi does not teach such limitation. Lindsley discloses that in a solid solution, compounds are molecularly dissolved in a solid matrix. Spray-dried dispersions (SDD) are a type of solid solution which has been used to increase the bioavailability of BCS class 2 and BCS class 4 drugs. Lindsley also teaches that SDD provide long-term stability and manufacturability ("[f]or example, shelf lives of more than 2 years have been demonstrated with SDDs."). SDD are obtained by dissolving the drug and polymer in an organic solvent and then spray-drying the solution (paragraph 0222).
Since Tacrolimus is a BCS class 2 drug, it would be obvious to one skilled in the art to dissolve the tacrolimus and a polymer in an organic solvent and spray-dry the solution to form a solid solution with a reasonable expectation of increasing the bioavailability of tacrolimus and providing long term stability and manufacturability.
Thus, Jenkins in view of Schiraldi and Lindsley teaches instant limitation wherein the macrolide in a molecularly dissolved non- nanoparticle form". Schiraldi's bioadhesive layer contains a homopolymer of ethylene oxide, which is instant mucoadhesive polymer. As discussed above, Schiraldi also teaches that its bioadhesive layer contains hydroxypropyl cellulose and a plasticizer (see claim 1). Schiraldi further teaches (claim 1) that a water-insoluble polymer, such as ethyl cellulose, propyl cellulose, polyethylene and polypropylene, can be included in the bioadhesive layer. It would be obvious to one skilled in the art to further include ethyl cellulose as the water-insoluble polymer in the bioadhesive layer with a reasonable expectation of success.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA S MERCIER whose telephone number is (571)272-9039. The examiner can normally be reached M-F 6:30 am to 4 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A Wax can be reached at 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MELISSA S MERCIER/Primary Examiner, Art Unit 1615
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